Low-Dose Decitabine Compared With Standard Supportive Care in Treating Older Patients With Myelodysplastic Syndrome

Leukemia Clinical Trial

Official title:

Intravenous Low-Dose Decitabine Versus Supportive Care in Elderly Patients With Primary Myelodysplastic Syndrome (MDS) (>10% Blasts or High-Risk Cytogenetics), Secondary MDS or Chronic Myelomonocytic Leukemia (CMML) Who Are Not Eligible for Intensive Therapy: An EORTC-German MDS Study Group Randomized Phase III Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00043134
• Other study ID #: CDR0000256224
• Secondary ID: EORTC-06011SUPER
• Status: Active, not recruiting
• Phase: Phase 3
• First received: August 5, 2002
• Last updated: April 10, 2010
• Start date: May 2002

Study information

• Verified date: April 2008
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Decitabine may help myelodysplasia cells develop into normal stem cells. It is not yet known if decitabine is more effective than standard supportive care in treating myelodysplastic syndrome.

PURPOSE: Randomized phase III trial to compare the effectiveness of low-dose decitabine with that of standard supportive care in treating older patients who have myelodysplastic syndrome.

Description:

OBJECTIVES:

• Compare the efficacy of low-dose decitabine vs standard supportive care, in terms of overall survival, of elderly patients with myelodysplastic syndromes.

• Compare the response rate and progression-free survival of patients treated with these regimens.

• Determine the toxicity of decitabine in these patients.

• Assess the duration of hospitalization and number of blood transfusions in patients treated with these regimens.

• Assess the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to cytogenetic risk factors (good vs poor vs intermediate vs unknown), disease (primary myelodysplastic syndrome (MDS) vs secondary MDS), and participating center. Patients with a successful cytogenetic exam are also stratified according to overall International Prognostic Scoring System score (intermediate 1 vs intermediate 2 vs high risk). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive decitabine IV over 4 hours every 8 hours for 3 days. Treatment repeats every 6 weeks for 4-8 courses in the absence of disease progression or unacceptable toxicity.

• Arm II: Patients receive standard supportive care. Quality of life is assessed at baseline, every 6 weeks during therapy, every 2 months for 1 year, and then every 3 months thereafter.

Patients are followed every 2 months for 1 year and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 220 patients (110 per treatment arm) will be accrued for this study within 2 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 220
• Est. primary completion date: May 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 60 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Diagnosis of primary or secondary myelodysplastic syndromes (MDS)

• Any FAB or WHO criteria cellular type allowed

• Bone marrow blast count on aspiration or biopsy of 1 of the following:

• No more than 10% with poor cytogenetic risk factors (defined as any numerical or structural abnormality of chromosome 7 and/or complex abnormalities)

• 11-20%

• 21-30% for patients with acute myeloid leukemia (AML) secondary to MDS (i.e., refractory anemia with excess blasts in transformation by FAB classification)

• Patients who failed the cytogenetic exam are allowed provided bone marrow blasts are at least 5% and/or 2-3 cytopenias are present

• No rapid progression towards full-blown AML

• No blast crisis of chronic myeloid leukemia

• No t(8;21) alone or in combination with other abnormalities

• Ineligible for intensive chemotherapy (e.g., cytarabine or an anthracycline)

PATIENT CHARACTERISTICS:

Age

• 60 and over

Performance status

• WHO 0-2

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics

Hepatic

• Bilirubin less than 1.5 times upper limit of normal (ULN)

• Hepatitis B surface antigen negative

Renal

• Creatinine less than 1.5 times ULN

Cardiovascular

• No severe cardiovascular disease

• No arrhythmias requiring chronic treatment

• No congestive heart failure

• No New York Heart Association class III or IV heart disease

• No symptomatic ischemic heart disease

Other

• HIV negative

• No active uncontrolled infection

• No other malignancy within the past 3 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix within the past 2 years

• No prior or concurrent evidence of CNS or psychiatric disorders requiring hospitalization

• No psychological, familial, sociological, or geographical condition that would preclude study

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 6 weeks since prior growth factors for primary MDS

• No concurrent antiangiogenic drugs (e.g., thalidomide)

• No concurrent interleukin, interferon, or anti-thymocyte globulin

Chemotherapy

• See Disease Characteristics

• More than 6 weeks since prior hydroxyurea for primary MDS

• No other prior chemotherapy for MDS or AML

• Prior chemotherapy for solid tumors or lymphoma (resulting in secondary MDS) allowed

Endocrine therapy

• No concurrent steroids (except as inhalation therapy)

Radiotherapy

• Prior radiotherapy for solid tumors or lymphoma (resulting in secondary MDS) allowed

Surgery

• Not specified

Other

• More than 6 weeks since prior immunosuppressive agents for primary MDS

• No concurrent amifostine

• No concurrent cyclosporine

• No other concurrent experimental therapies

Study Design

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myelomonocytic, Chronic
• Myelodysplastic Syndromes
• Myelodysplastic-Myeloproliferative Diseases
• Myelodysplastic/Myeloproliferative Neoplasms
• Myeloproliferative Disorders
• Preleukemia
• Syndrome

Intervention

Drug:
• decitabine

Locations

Country	Name	City	State
Austria	Innsbruck Universitaetsklinik	Innsbruck
Austria	St. Johanns-Spital	Salzburg
Belgium	Institut Jules Bordet	Brussels
Belgium	U.Z. Gasthuisberg	Leuven
Belgium	H. Hartziekenhuis - Roeselaere.	Roeselare
Belgium	Centre Hospitalier Peltzer-La Tourelle	Verviers
Croatia	University Hospital Rebro	Zagreb
Czech Republic	First Medical Clinic of Charles University Hospital	Prague
Czech Republic	Institute of Hematology and Blood Transfusion	Prague
Germany	Charite University Hospital - Campus Virchow Klinikum	Berlin
Germany	Staedtisches Klinikum Braunschweig	Braunschweig
Germany	DIAKO Ev. Diakonie Krankenhaus gGmbH	Bremen
Germany	Universitatsklinikum Carl Gustav Carus	Dresden
Germany	St. Johannes Hospital - Medical Klinik II	Duisburg
Germany	St. Antonius Hospital	Eschweiler
Germany	Klinikum der J.W. Goethe Universitaet	Frankfurt
Germany	Klinikum der Albert - Ludwigs - Universitaet Freiburg	Freiburg
Germany	Universitaetsklinikum Freiburg	Freiburg
Germany	Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet	Greifswald
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Ruprecht - Karls - Universitaet Heidelberg	Heidelberg
Germany	Universitaetsklinikum des Saarlandes	Homburg
Germany	Westpfalz-Klinikum GmbH	Kaiserslautern
Germany	Onkologische Schwerpunktpraxis - Leer	Leer
Germany	Sana Kliniken Luebeck	Luebeck
Germany	Kreiskrankenhaus Luedenscheid	Luedenscheid
Germany	Klinikum der Universitaet Muenchen - Grosshadern Campus	Munich
Germany	Klinikum Rechts Der Isar - Technische Universitaet Muenchen	Munich
Germany	Staedtisches Krankenhaus Muenchen - Harlaching	Munich
Germany	Robert-Bosch-Krankenhaus	Stuttgart
Germany	Southwest German Cancer Center at Eberhard-Karls-University	Tuebingen
Germany	Klinikum Der Stadt Villingen - Schwenningen	Villingen-Schwenningen
Germany	Medizinische Poliklinik, Universitaet Wuerzburg	Wuerzburg
Italy	Universita Degli Studi di Florence - Policlinico di Careggi	Florence
Italy	Azienda Ospedaliera Vito Fazzi	Lecce
Italy	Azienda Ospedale - d S. Salvatore	Pesaro
Italy	Istituto Regina Elena	Rome
Italy	Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore	Rome
Netherlands	HagaZiekenhuis - Locatie Leyenburg	's-Gravenhage
Netherlands	Onze Lieve Vrouwe Gasthuis	Amsterdam
Netherlands	Leiden University Medical Center	Leiden
Netherlands	Academisch Ziekenhuis Maastricht	Maastricht
Netherlands	Universitair Medisch Centrum St. Radboud - Nijmegen	Nijmegen
Switzerland	Kantonsspital - Abteilung Onkologie	Basel
Turkey	Ibn-i Sina Hospital	Ankara
United Kingdom	Royal South Hants Hospital	Southampton	England

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Countries where clinical trial is conducted

Austria,  Belgium,  Croatia,  Czech Republic,  Germany,  Italy,  Netherlands,  Switzerland,  Turkey,  United Kingdom, 

References & Publications (1)

WijerMans P, Suciu S, Baila L, et al.: Low dose decitabine versus best supportive sare in elderly patients with intermediate or high risk MDS not eligible for intensive chemotherapy: final results of the randomizedpPhase III study (06011) of the EORTC Leu

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Duration of overall survival			No
Secondary	Best response rate as measured by Cheson response criteria			No
Secondary	Overall progression-free survival			No
Secondary	Toxicity as assessed by CTC v2.0			Yes
Secondary	Quality of life as assessed by EORTC QLQ30			No
Secondary	Days in Hospital			No